WO2005033089A1 - Sel d'acide 6-(1, 3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoique avec du diamide de n, n-dimethyl-imidodicarbonimidique - Google Patents

Sel d'acide 6-(1, 3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoique avec du diamide de n, n-dimethyl-imidodicarbonimidique Download PDF

Info

Publication number
WO2005033089A1
WO2005033089A1 PCT/IN2003/000329 IN0300329W WO2005033089A1 WO 2005033089 A1 WO2005033089 A1 WO 2005033089A1 IN 0300329 W IN0300329 W IN 0300329W WO 2005033089 A1 WO2005033089 A1 WO 2005033089A1
Authority
WO
WIPO (PCT)
Prior art keywords
methyl
isobenzofuranyl
dihydro
oxo
methoxy
Prior art date
Application number
PCT/IN2003/000329
Other languages
English (en)
Inventor
Sambasivam Ganesh
Goutam Das
Shankara Rao Arvind Atignal
Kiran Mazumdar-Shaw
Original Assignee
Biocon Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Biocon Limited filed Critical Biocon Limited
Priority to PCT/IN2003/000329 priority Critical patent/WO2005033089A1/fr
Priority to AU2003272083A priority patent/AU2003272083A1/en
Publication of WO2005033089A1 publication Critical patent/WO2005033089A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
    • C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection

Definitions

  • 6-(l,3 ⁇ dihydro-4-hydroxy-6-methoxy-7-methyl-3- oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid, sodium salt or its 2-ethyl morphoiino derivative is used as immunosuppressants.
  • 6- (l,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5- isobenzofuranyl)-4-methyl-4-hexenoic acid is generally administered as a sodium salt or 2-ethyl morphoiino derivative so that active free acid is made available for absorption.
  • Antihyperglycemic agents are used for treatment of diabetes.
  • N, N- dimethyl- imidodicarbonimidic diamide is used for treatment of Non-insulin dependent diabetes mellitus (NIDDM).
  • N, N-dimethyl- imidodicarbonimidic diamide is generally administered a HCI salt.
  • the present inventions discloses a novel compound of formula I which can be simultaneously used as an immunosuppressant and antihyperglycemic agent for the treatment of diabetic nephropathy.
  • SUMMARY OF THE INVENTION The present invention discloses a novel compound of formula I. The compound can be simultaneously used as an immunosuppressant and antihyperglycemic agent for the treatment of diabetic nephropathy.
  • FORMULA I The important embodiment of the invention is that the compound of formula I, wherein the two drug molecules form a mutual salt which can be called X N, N-dimethyl- imidodicarbonimidic diamide salt of 6-(l,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3- oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid.
  • the invention discloses the compound of formula I, wherein the 6-(l,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5- isobenzofuranyl)-4-methyl-4-hexenoic acid is an immunosuppressive drug and N, N-dimethyl- imidodicarbonimidic diamide is an antihyperglycemic drug.
  • the compound of formula I is formed when the two compounds are treated with each other under suitable conditions to form a non-covalent bond between the carboxylic group of 6- (l,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5- isobenzofuranyl)-4-methyl-4-hexenoic acid and nitrogen of N, N- dimethyl- imidodicarbonimidic diamide.
  • the non- covalent bond thus formed is an ionic bond between 6-(l,3- dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)- 4-methyl-4-hexenoic acid and N, N-dimethyl- imidodicarbonimidic diamide.
  • the compound of formula I is a mutual salt of 6-(l,3- dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)- 4-methyl-4-hexenoic acid and N, N-dimethyl- imidodicarbonimidic diamide.
  • compound of formula I retain the free acid form of 6-(l,3-dihydro- 4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl- 4-hexenoic acid.
  • Compound of formula I have the extra advantage of delivering the free acid form of 6-( ⁇ ,3-dihydro-4-hydroxy-6- methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid without employing any metal cation. Unlike prior art, compound of formula I delivers N, N- dimethyl- imidodicarbonimidic diamide free-base without employing any other acid salt like hydrochloride salt.
  • the following non-limiting examples illustrate the inventors' preferred method for preparing the compound of the invention.
  • reaction mixture was chilled (10-15° C) and filtered to afford the mutual salt of 6-(l,3-dihydro-4-hydroxy-6- methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic5 acid and N, N-dimethyl- imidodicarbonimidic diamide.
  • Example 2 To a solution of 6-(l,3-dihydro-4-hydroxy-6-methoxy-7- methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid (10 g, 0.03 mol) in isobutyl acetate (75 ml), N, N-dimethyl-o imidodicarbonimidic diamide free base (4.0 g, 0.03 mol) was added and stirred.
  • reaction mixture was chilled (10-15° C) and filtered o afford the mutual salt of 6-(l,3-dihydro-4-hydroxy-6-methoxy-7- methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid and N, N-dimethyl- imidodicarbonimidic diamide.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Diabetes (AREA)
  • Transplantation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un nouveau composé représenté par la formule générale (I), un sel mutuel d'acide 6-(1,3--dihydro-4-hydroxy-6-méthoxy-7-méthyl-3-oxo-5-isobenzofuranyl)-4-méthyl-4-hexénoïque et de diamide de N, N-diméthyl-imidodicarbonimidique. Le composé représenté par la formule générale (I) peut être simultanément utilisé comme agent immunosuppresseur et anti-hyperglycémique pour le traitement de la néphropathie diabétique.
PCT/IN2003/000329 2003-10-07 2003-10-07 Sel d'acide 6-(1, 3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoique avec du diamide de n, n-dimethyl-imidodicarbonimidique WO2005033089A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/IN2003/000329 WO2005033089A1 (fr) 2003-10-07 2003-10-07 Sel d'acide 6-(1, 3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoique avec du diamide de n, n-dimethyl-imidodicarbonimidique
AU2003272083A AU2003272083A1 (en) 2003-10-07 2003-10-07 Salt of 6-(1, 3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid with n, n-dimethyl-imidodicarbonimidic diamide

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IN2003/000329 WO2005033089A1 (fr) 2003-10-07 2003-10-07 Sel d'acide 6-(1, 3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoique avec du diamide de n, n-dimethyl-imidodicarbonimidique

Publications (1)

Publication Number Publication Date
WO2005033089A1 true WO2005033089A1 (fr) 2005-04-14

Family

ID=34401267

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2003/000329 WO2005033089A1 (fr) 2003-10-07 2003-10-07 Sel d'acide 6-(1, 3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoique avec du diamide de n, n-dimethyl-imidodicarbonimidique

Country Status (2)

Country Link
AU (1) AU2003272083A1 (fr)
WO (1) WO2005033089A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008003637A2 (fr) * 2006-07-05 2008-01-10 Dsm Ip Assets B.V. Isolation et utilisation de sels aminés d'acide mycophénolique
US7683188B2 (en) 2004-04-26 2010-03-23 TEVA Gyógyszergyár Zártkōrūen Mūkōdō Részvénytársaság Process for preparation of mycophenolic acid and ester derivatives thereof
WO2010146604A2 (fr) 2009-06-18 2010-12-23 Exemed Pharmaceuticals Procédés de préparation de chlorhydrate de metformine

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4948793A (en) * 1987-01-30 1990-08-14 Syntex (U.S.A.) Inc. Treatment of autoimmune diseases with the morpholinoethyl ester of mycophenolic acid, and derivatives thereof
WO2003011273A1 (fr) * 2001-07-31 2003-02-13 The Governement Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services Metformine utilisee dans le traitement de conditions hyperglycemiques

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4948793A (en) * 1987-01-30 1990-08-14 Syntex (U.S.A.) Inc. Treatment of autoimmune diseases with the morpholinoethyl ester of mycophenolic acid, and derivatives thereof
WO2003011273A1 (fr) * 2001-07-31 2003-02-13 The Governement Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services Metformine utilisee dans le traitement de conditions hyperglycemiques

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7683188B2 (en) 2004-04-26 2010-03-23 TEVA Gyógyszergyár Zártkōrūen Mūkōdō Részvénytársaság Process for preparation of mycophenolic acid and ester derivatives thereof
WO2008003637A2 (fr) * 2006-07-05 2008-01-10 Dsm Ip Assets B.V. Isolation et utilisation de sels aminés d'acide mycophénolique
WO2008003637A3 (fr) * 2006-07-05 2008-05-08 Dsm Ip Assets Bv Isolation et utilisation de sels aminés d'acide mycophénolique
WO2010146604A2 (fr) 2009-06-18 2010-12-23 Exemed Pharmaceuticals Procédés de préparation de chlorhydrate de metformine

Also Published As

Publication number Publication date
AU2003272083A1 (en) 2005-04-21

Similar Documents

Publication Publication Date Title
US7638627B2 (en) Process of preparing imatinib and imatinib prepared thereby
US11622942B2 (en) Benzene-1,3,5-tricarboxamide derived ester lipids and uses thereof
US11718611B2 (en) Benzenesulfonylbenazamide compound for inhibiting BCL-2 protein and composition and use thereof
US7803942B2 (en) Crystals of morphinan derivative and process for producing the same
WO2010146604A2 (fr) Procédés de préparation de chlorhydrate de metformine
US20080045707A1 (en) Processes for the preparation of linezolid intermediate
EP2625162A1 (fr) Procédés de fabrication d'acétate de phényle de l-ornithine
WO2005023766A1 (fr) Sel d'atorvastatine associee a de la metformine
US8153672B2 (en) Polymorphic forms of deferasirox (ICL670A)
US6531509B2 (en) Stable gabapentin containing more than 20 ppm of chlorine ion
US20040147607A1 (en) Stable gabapentin having pH within a controlled range
AU2001266992A1 (en) Stable gabapentin having pH within a controlled range
WO2005033089A1 (fr) Sel d'acide 6-(1, 3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoique avec du diamide de n, n-dimethyl-imidodicarbonimidique
CN115461344A (zh) 一种glp-1受体激动剂的晶型a及其制备方法
WO2006086773A2 (fr) Analogues de polyamine en tant que modulateurs de la migration cellulaire et de la motilite cellulaire
WO2005033067A1 (fr) Sel de l'acide 1,2,6,7,8,8a-hexahydro-?,?,6-trihydroxy-2-methyl-8-[(2s)-2-methyl-1-oxobutoxy]-, (?r,? r,1s,2s,6s,8s,8ar)- 1-naphthaleneheptanoique et d'un diamide n,n-dimethyl-imidodicarbonimidique
US20100069443A1 (en) Compound with benzamide skeleton having cyclooxygenase-1 (cox-1)-selective inhibitory activity
AU2019349414B2 (en) Process for preparing the compound 2,2-difluoro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(6-(S-methylsulfonimidoyl)pyridin-3-yl)phenyl)propan-2-yl)acetamide
RU2389491C2 (ru) Комплекс, содержащий меквитазин (mequitazine), циклодекстрин и агент взаимодействия
US10081605B2 (en) Synthesis of cyclocreatine and analogs thereof
JPS63255268A (ja) ドーパミン−β−ヒドロキシラーゼ抑制剤
KR101653816B1 (ko) 결정형 사포그릴레이트 옥살산염 일수화물 또는 이의 무수물
CN1489578A (zh) 3-(3-脒苯基)-5-[({[1-(1-亚氨基乙基)-4-哌啶基]甲基}氨基)甲基]苯甲酸二盐酸盐及其制备方法
KR860000999B1 (ko) N(2,6-디클로로페닐)아세트아미딘의 제조방법
CA2859156A1 (fr) Traitement du diabete de type i et de type ii

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PG PH PL PT RO RU SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP